In a chemical process, in the case where a sequential mixture and separation operation can be carried out with ease, sequential work efficiency can be dramatically increased. Presently, it is known that change in temperature causes phase solving/phase separation in a solvent mixture that is formed of a combination of a solvent having a perfluoroalkyl group, and a general organic solvent (I. T. Horvath, J. Rabai, Science, 1994, 266, 72; J. A. Gladysz, Science, 1994, 266, 55).
Japanese Unexamined Patent Publication H15 (2003)-62448 shows a combination of a cycloalkane and a polar solvent as an example of a solvent mixture where phase solving/phase separation is caused. Such solution phase solving and separation phenomena, where phase solving and phase separation can be made to repeat by slightly changing the temperature, can be applied to a wide range of chemical processes, from the micro and macro scale to the plant level. Recently, a method for making a number of processes progress simultaneously, where combinatorial chemistry or a high throughput process method is carried out in a tabletop apparatus, is used widely in many test and research institutions.
FIG. 4 is a conceptual diagram illustrating the theory that solvent mixture causes phase solving/phase separation. (A) in FIG. 4 shows a state where single organic solvents or mixed organic solvents are separated. For example, a solvent that dissolves a reactive material is used as one solvent, and a solvent that dissolves a catalyst or a reaction adjuvant is used as the other solvent. (B) is a step where reaction progresses under such temperature conditions that the solvent is in a state where a uniform phase solving mixture solvent system. (C) shows the state of a separated solvent system where solvent phases of which the main components are solvents that form reversible solvent systems under the above described temperature conditions are separated into phases in which products are dissolved and catalysts or a reaction adjuvant are dissolved. Then, the phase in which the products are dissolved (product solution) is separated and taken out so as to be used for a desired application, while the phase in which reaction adjuvant dissolves (catalyst or reaction adjuvant solution) is recycled (D).
One example of an automatic synthesizing method which uses the theory that such a solvent system causes phase solving/phase separation is described in reference to FIG. 3. That is to say, a material such as a reagent is injected into a reaction container 11 using a sampling apparatus 12 so that a two-phase solution (I) is gained. Next, reaction container 11 is heated, so that the two-phase solution becomes a uniform solution where reaction starts (II). After reaction has started and a predetermined period of time has passed, cooling is started (III). The solution in reaction container 11 automatically separates into phases when the temperature has been lowered to a predetermined temperature or lower (IV). Next, the product phase in reaction container 11 is extracted using an extraction apparatus 17 (V), and this product solution 16 is used for animal experimentation, which is an activity assay, or used for analysis (VI). According to a method for making a number of processes progress simultaneously, several tens to one hundred or more reaction systems, one of which is, for example, that shown in FIG. 3, are carried out in the same apparatus and under the same reaction conditions.
However, it is structurally very troublesome to individually control the temperature of several tens to one hundred or more containers in a tabletop apparatus. Therefore, an apparatus where a block heater which can heat all of the several tens to one hundred or more containers simultaneously is built in is conventionally used. In this case, an automatic sampling operation is carried out on each sample sequentially and automatically, and after that, all the containers are simultaneously heated. In addition, after the solution has been converted into a uniform solution and reaction is complete, all the containers are cooled simultaneously. According to this method, the period of time that is required from the start of the automatic sampling operation to the start of the heating differs, depending on the container. After the automatic sampling, though the solution is in a two-phase state before the start of the reaction, in which, theoretically, no reaction occurs, in reality, a slight amount of reaction occurs even in the two-phase state, since there is contact between the phases in the interface portion. As described above, all of the process conditions are different, depending on the container, according to the conventional method, and it is impossible to carry out the process under the same conditions. This has caused many problems with reproducibility in chemical processes.
Meanwhile, in the case where a multi-stage successive reaction process is carried out by repeating successive phase solving/phase separation, the temperature of the reaction containers should be increased or lowered at each stage, and thereby, the temperature of the solution changes, so that the phase structure of the solution changes. This causes a problem, such that control becomes difficult, particularly on a plant scale, where the capacity is large. In addition, when the temperature of the reaction containers on a plant scale is increased or lowered at each stage, a problem arises, such that the amount of use of utilities, such as electrical power and cooling water, becomes massive, increasing the cost for manufacture.
Accordingly, an object of the present invention is to provide a method for making a two-phase solution of which the phase state changes as a result of temperature conversion react in a number of processes, where a chemical process can be carried out on a number of samples under the same conditions in one processing apparatus, and which is excellent in operativity and reproducibility, as well as an apparatus for implementing this. In addition, another object of the present invention is to provide a method for making a two-phase solution of which the phase state changes due to temperature conversion which is excellent in operativity and efficiency in production, as well as an apparatus for implementing this.    (Non-Patent Document 1) I. T. Horvath, J. Rabai, Science, 1994, 266, 72; J. A. Gladysz, Science, 1994, 266, 55    (Patent Document 1) Japanese Unexamined Patent Publication H15 (2003)-62448 (Claim 1)